Optimal Maintenance Strategy After Anti-EGFR-Based Induction Therapy in Metastatic Colorectal Cancer

Alessandra Raimondi, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, discusses results from an individual patient data pooled analysis of the Valentino and Panama clinical trials exploring the optimal maintenance treatment strategy following anti-EGFR-based induction therapy for patients with RAS wild type metastatic colorectal cancer.

The Valentino trial demonstrated inferior progression-free survival (PFS) with single-agent panitumumab after 4 months of FOLFOX plus panitumumab induction than with FUFA plus panitumumab, single-agent panitumumab was associated with slightly reduced toxicity.

The Panama trial demonstrated significantly superior PFS with FUFA plus panitumumab after 3 months of FOLFOX plus panitumumab induction than with FUFA alone.

Findings from this analysis were presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

I am Alessandra Raimondi. I'm a medical oncologist and I work at the National Cancer Institute of Milan, Italy. I'm here at ESMO World GI to present the results of our work.

It is about an individual patient data pooled analysis of 2 studies, the Valentino and Panama trials, on the optimal maintenance strategy after an anti-EGFR-based first-line induction in RAS wild type metastatic colorectal cancer. In metastatic colorectal cancer, the optimal maintenance strategy after bevacizumab-based first-line therapy is a combination of fluoropyrimidine plus bevacizumab. Anti-EGFR agents plus double chemotherapy is considered the guideline-endorsed first-line option in RAS and BRAF wild type metastatic colorectal cancer patients. Several randomized phase 2 trials investigated maintenance or intensification strategies after anti-EGFR-based induction. However, due to the limited sample size of the studies and the heterogeneous design, the optimal strategy has not been clearly defined yet. We performed individual patient data pooled analysis of the Valentino and Panama trials.

Valentino was a multi-center, randomized phase 2 trial that enrolled RAS wild type metastatic colorectal cancer patients who were randomized to 8 cycles of FOLFOX plus panitumumab induction, followed by maintenance with 5-flouroutacil and leucovorin plus panitumumab, or the same induction followed by maintenance with single-agent panitumumab. Panama was a multi-center randomized phase 2 trial that enrolled RAS wild type metastatic colorectal cancer patients who achieved disease control after 6 cycles of FOLFOX responding induction, and they were randomized to receiving maintenance with 5-flouroutacil and leucovorin alone or with panitumumab.

Only patients who received maintenance as per protocol were included in the study. And they were stratified according to the maintenance treatment arm: combination with 5-flouroutacil and leucovorin plus panitumumab, or monotherapy, either 5-flouroutacil and leucovorin or panitumumab. The aim of our study was to investigate the optimal maintenance strategy after an anti-EGFR-based first-line induction.

To this purpose, we calculated progression-free survival and overall survival from the start of maintenance and toxicity only during maintenance phase. Overall 79, 123, and 210 patients received maintenance with single agent panitumumab, single agent 5-flouroutacil and leucovorin, or combination of 5-flouroutacil and leucovorin plus panitumumab respectively. The baseline patients and disease characteristics were well-balanced between the three arms. Except for ECOG performance status, with the slight prevalence of PS-0 in the single-agent panitumumab arm.

For what concerns the survival outcomes, we reported a significantly superior progression-free survival in combination as compared to monotherapy. Medium PFS was 9.0 and 5.8 months, in combination as compared to monotherapy, with an hazard ratio of 0.77, and a significant P value of 0.016. Median overall survival was 28.0 and 26.1 months in combination and monotherapy respectively, with a non-significant 13% reduction in the risk of death.

The safety profile was consistent with the singular trial records and the differential distribution of anti-EGFR and chemotherapy-related toxicity. However, we reported an increase of any grade any adverse event in combination on maintenance treatment.

In conclusion, in this pooled analysis of 2 randomized clinical trial after an anti-EGFR-based induction chemotherapy, the combination maintenance treatment with 5-flouroutacil and leucovorin plus panitumumab was superior in terms of PFS compared to maintenance with monotherapy, either 5-flouroutacil and leucovorin or panitumumab. These results are consistent with the guideline-endorsed maintenance treatment after a bevacizumab-based combination chemotherapy. However, they deserve further confirmation. And, to this purpose, we are performing a larger individual patient data pooled analysis, including other pivotal clinical trials on maintenance or intensification strategies after an anti-EGFR-based induction. In order to achieve more robust results, especially in terms of overall survival. Thank you very much for listening.

Source:

Raimondi A, Morano F, Trarbach T, et al. Optimal maintenance treatment strategy following an anti-EGFR-based first-line induction therapy in patients with RAS wild type metastatic colorectal cancer: An individual patient data pooled analysis of clinical trials. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract SO-21.